The role of cell surface gangliosides in promotion of transformation in "promotable" JB6 mouse epidermal cells is being studied. We have previously reported that there is a substantial decrease in cellular membrane trisialoganglioside (GT) synthesis in response to 12-O-tetradecanoylphorbol-13-acetate (TPA) in the TPA-sensitive, promotable cells, but not in the resistant counterparts. To understand the mechanism of the promotion-relevant decrease in GT synthesis, an oxidative degradation pathway of sialoglycoconjugate was investigated. To study the effect of specific oxidation of cell surface sialic acid, sodium meta periodate (NaI04) was used. When oxidized by NaI04, JB6 cells were transformed. This transformation was inhibited by retinoic acid and other sialoglycoconjugates. Since TPA produces elevated reactive oxygen moieties it is hypothesized that cell surface glycolipids may be targets. Another mouse skin promoter, benzoyl peroxide (a generator of reactive oxygen), was entrapped in liposomes and found to induce promotion of transformation in JB6 cells. This promotion of transformation was not inhibited by retinoic acid but was inhibited by the ganglioside GT. Continuing efforts are aimed at isolation of JB6 cells that are resistant to the GT response to TPA. A requirement for the GT response in promotion would suggest that these variants should be promotion-resistant. A new cell line has been developed from parental JB6 cells which is resistant to low glutamine concentrations and is also resistant to the GT response to TPA. In addition, this cell line appears to have been coselected for promotion resistance, thus arguing further for a causal relationship of the GT synthesis response to TPA to promotion of neoplastic transformation. In a collaborative study the synthesis of asialo GM1 in stimulated macrophages was correlated to the order of stimulation and binding of fluoresceinated antibody to asialo GM1.